Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the human brain. It has contributed greatly to our understanding of normal brain function and shows promise in therapies for psychiatric and neurological disorders. Exactly what TMS does to neuronal activity, however, remains unknown. We will apply single pulses of TMS while recording from single neurons in behaving non-human primates. Our TMS methods will correspond to those used in humans and will be easily adoptable by any primate neurophysiology laboratory. A team of researchers will design custom TMS coils to direct the focus of stimulation to precise locations of cerebral cortex, innovative electronics to permit neuronal recordings within 1 ms after TMS pulses, and controlled visual- oculomotor tasks to allow systematic variation of behavioral and thus neuronal state. We will record from single neurons and field potentials at both the site of stimulation and at distant but monosynaptically connected sites. The end result of our work will be to discover how TMS influences the brain at the level of single neurons and simple circuits. Implications will include improved, physiologically-guided TMS protocols for human basic research studies and therapeutic applications. PUBLIC HEALTH RELEVANCE: Non-invasive stimulation of the human brain using magnetic pulses near the head (transcranial magnetic stimulation or TMS) is a valuable tool for studying vision, cognition, and movement, but exactly how TMS affects brain activity is an open question. The proposed work will answer this question by recording from single neurons in the brains of behaving primates during TMS. The project is a technical challenge but its feasibility has been confirmed, its inherent risks will be managed by a team of wide-ranging experts, and its end result will be transformative: data on the physiological mechanisms of TMS will improve basic research on the human brain and help clinicians fulfill the promise of TMS as an effective therapeutic intervention.